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Semiconductor nanocrystal probes for biological applications

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Publication number
CA2366303A1
CA2366303A1 CA 2366303 CA2366303A CA2366303A1 CA 2366303 A1 CA2366303 A1 CA 2366303A1 CA 2366303 CA2366303 CA 2366303 CA 2366303 A CA2366303 A CA 2366303A CA 2366303 A1 CA2366303 A1 CA 2366303A1
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Patent type
Prior art keywords
semiconductor
linking
energy
capable
agents
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Granted
Application number
CA 2366303
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French (fr)
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CA2366303C (en )
Inventor
Shimon Weiss
Marcel Bruchez
Paul Alivisatos
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California
Original Assignee
Shimon Weiss
Marcel Bruchez
Paul Alivisatos
The Regents Of The University Of California
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    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H01L33/00Semiconductor devices with at least one potential-jump barrier or surface barrier specially adapted for light emission; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L33/005Processes
    • H01L33/0062Processes for devices with an active region comprising only III-V compounds
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/02Use of particular materials as binders, particle coatings or suspension media therefor
    • C09K11/025Use of non-luminescent materials other than binders
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/56Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing sulfur
    • C09K11/562Chalcogenides
    • C09K11/565Chalcogenides with zinc cadmium
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/88Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing selenium, tellurium or unspecified chalcogen elements
    • C09K11/881Chalcogenides
    • C09K11/883Chalcogenides with zinc or cadmium
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/89Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing mercury
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; MISCELLANEOUS COMPOSITIONS; MISCELLANEOUS APPLICATIONS OF MATERIALS
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/89Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing mercury
    • C09K11/892Chalcogenides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6816Hybridisation assays characterised by the means of detection
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay
    • G01N33/531Production of immunochemical test materials
    • G01N33/532Production of labelled immunochemicals
    • G01N33/533Production of labelled immunochemicals with fluorescent label
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay
    • G01N33/536Immunoassay; Biospecific binding assay with immune complex formed in liquid phase
    • G01N33/542Immunoassay; Biospecific binding assay with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay
    • G01N33/543Immunoassay; Biospecific binding assay with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54373Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/588Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with semiconductor nanocrystal label, e.g. quantum dots
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01LSEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H01L33/00Semiconductor devices with at least one potential-jump barrier or surface barrier specially adapted for light emission; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L33/005Processes
    • H01L33/0083Processes for devices with an active region comprising only II-VI compounds
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2563/00Nucleic acid detection characterised by the use of
    • C12Q2563/107Nucleic acid detection characterised by the use of fluorescence
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/14Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/141111Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/14Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222Hetero-O [e.g., ascorbic acid, etc.]

Abstract

A semiconductor nanocrystal compound capable of linking to one or more affinity molecules comprising (1) one or more semiconductor nanocrystals capable of, in response to exposure to a first energy, providing a second energy, and (2) one or more linking agents, having a first portion linked to the one or more semiconductor nanocrystals and a second portion capable of linking to one or more affinity molecules. One or more of semiconductor nanocrystal compounds linked to one or more affinity molecules to form a semiconductor nanocrystal probe capable of bonding with one or more detectable substances in a material being analyzed, and are capable of, in response to exposure to a first energy, providing a second energy. The probe is capable of emitting electromagnetic radiation in a narrow wavelength band and/or absorbing, scattering, or diffracting energy when excited by an electromagnetic radiation source of narrow or broad bandwidth, or a particle beam. The probe is stable to repeated exposure to energy in the presence of oxygen and/or other radicals.

Claims (25)

1. A semiconductor nanocrystal compound capable of linking to one or more affinity molecules and capable of, in response to exposure to a first energy from a proximal source, providing a second energy, said semiconductor nanocrystal compound comprising:
a) one or more semiconductor nanocrystals, each capable of, in response to exposure to said first energy, providing said second energy; and b) one or more first linking agents, at least a portion of which said linking agents are linked to said one or more semiconductor nanocrystals, each of said one or more first linking agents are capable of linking to (i) one or more second linking agents or (ii) one or more affinity molecules.
2. The semiconductor nanocrystal compound of claim 1 wherein the proximal source is a first semiconductor nanocrystal.
3. The semiconductor nanocrystal compound of claim 1 wherein at least one of said one or more first linking agents comprises a three-dimensional shaped structure capable of having linked thereto said one or more semiconductor nanocrystals.
4. The semiconductor nanocrystal compound of claim 3 wherein said three-dimensional shaped structure comprises a medium transparent to, capable of transferring or both transparent to and capable of transferring:
i) said first energy to which said one or more semiconductor nanocrystals is exposed; and ii) said second energy provided by said semiconductor nanocrystals in response to said exposure to said first energy.
5. A semiconductor nanocrystal compound capable of linking to one or more affinity molecules and capable of, in response to exposure to a first energy, providing a second energy, said semiconductor nanocrystal compound comprising:
a) one or more semiconductor nanocrystals, each capable of, in response to exposure to said first energy, providing said second energy; and b) one or more first linking agents, at least a portion of which said linking agents are linked to said one or more semiconductor nanocrystals, each of said one or more first linking agents are capable of linking to (i) one or more second linking agents or (ii) one or more affinity molecules, wherein at least one of said one or more first linking agents comprises a three-dimensional shaped structure capable of having linked thereto said one or more semiconductor nanocrystals.
6. A semiconductor nanocrystal probe capable of, in response to a first energy from a proximal source, providing a second energy, comprising:
a) one or more semiconductor nanocrystal compounds;
and b) one or more affinity molecules linked to said one or more semiconductor nanocrystal compounds.
7. A semiconductor nanocrystal probe capable of bonding with one or more detectable substances and capable of, in response to exposure to a first energy from a proximal source, providing a second energy, said semiconductor nanocrystal probe comprising:
a) one or more semiconductor nanocrystals, each capable of, in response to exposure to said first energy, providing said second energy;
b) one or more first linking agents, to which said one or more semiconductor nanocrystals are linked, each of said one or more first linking agents capable of linking to:
i) one or more second linking agents; or ii) one or more affinity molecules; and c) one or more affinity molecules linked either to said one or more second linking agents or to said one or more first linking agents, each of said one or more affinity molecules capable of selectively bonding to said one or more detectable substances.
8. The semiconductor nanocrystal probe of claim 7 wherein at least one of said one or more semiconductor nanocrystals comprise:
a) a core; and b) one or more shells, concentrically disposed around the core.
9. A semiconductor nanocrystal probe capable of bonding with one or more detectable substances and capable of, in response to exposure to a first energy, providing a second energy, comprising:
a) one or more semiconductor nanocrystals, each capable of, in response to exposure to said first energy, providing said second energy;
b) one or more first linking agents, at least one of said one or more first linking agents comprising a three-dimensional shaped structure capable of having linked thereto said one or more semiconductor nanocrystals, each of said one or more first linking agents capable of linking to:
i) one or more second linking agents; or ii) one or more affinity molecules; and c) one or more affinity molecules linked either to said one or more second linking agents or to said one or more first linking agents, each of said one or more affinity molecules capable of selectively bonding to said one or more detectable substances.
10. The modified semiconductor nanocrystal probe of claim 6, 7 or 9 wherein said one or more affinity molecules comprise one or more strands of nucleic acid.
11. The semiconductor nanocrystal probe of claim 6, 7 or 9 wherein said one or more affinity molecules comprise one or more first protein molecules.
12. The semiconductor nanocrystal probe of claim 6, 7 or 9 wherein said one or more affinity molecules comprise one or more small molecules.
13. The semiconductor nanocrystal probe of claim 9 wherein said three-dimensional shaped structure comprises a medium transparent to, capable of transferring or both transparent to and capable of transferring:
a) said first energy to which said one or more semiconductor nanocrystals is exposed; and b) said second energy provided by said semiconductor nanocrystals in response to said exposure to said first energy.
14. The semiconductor nanocrystal probe of claim 9 wherein each of said one or more affinity molecules comprises a molecule of one or more strands of nucleic acid, and each of said one or more detectable substances comprises a molecule of one or more strands of nucleic acid with which said probe bonds.
15. A process for forming a semiconductor nanocrystal compound capable of linking to one or more affinity molecules and capable of, in response to exposure to a first energy, providing a second energy, said semiconductor nanocrystal compound, said process comprising linking together:
a) one or more semiconductor nanocrystals, each capable of, in response to exposure to said first energy, providing said second energy; and b) one or more linking agents, wherein said step of linking said one or more semiconductor nanocrystals to said one or more first linking agents further comprises linking said one or more semiconductor nanocrystals to one or more three-dimensional shaped structures comprising said one or more first linking agents.
16. A process for forming a semiconductor nanocrystal probe capable of bonding with one or more detectable substances and capable of, in response to exposure to a first energy, providing a second energy, said process comprising the steps of:
a) linking one or more first linking agents with one or more semiconductor nanocrystals, said semiconductor nanocrystals each capable of, in response to exposure to said first energy, providing said second energy;
and b) linking said one or more first linking agents to either:
i) one or more second linking agents; or ii) one or more affinity molecules capable of selectively bonding to said one or more detectable substances; and c) linking said one or more affinity molecules to said one or more second linking agents when said one or more first linking agents are linked to said one or more second linking agents, wherein said step of linking said one or more semiconductor nanocrystals to said one or more first linking agents further comprises linking said one or more semiconductor nanocrystals to one or more three-dimensional shaped structures comprising said one or more first linking agents.
17. A process for treating a material by introducing one or more semiconductor nanocrystal probes into said material which comprises:

a) contacting said material with one or more semiconductor nanocrystal probes, said one or more semiconductor nanocrystal probes each comprising:

i) one or more semiconductor nanocrystals, each capable of, in response to exposure to a first energy, providing a second energy;
ii) one or more first linking agents, to which said one or more semiconductor nanocrystals are linked, each of said one or more first linking agents capable of linking to:
a) one or more second linking agents; or b) one or more affinity molecules; and iii) one or more affinity molecules linked either to said one or more second linking agents or to said one or more first linking agents;

b) exposing said one or more semiconductor nanocrystal probes in said material to said first energy whereby said second energy is provided by said one or more semiconductor nanocrystals in said one or more semiconductor nanocrystal probes;
c) transferring said second energy from said one or more semiconductor nanocrystal probes to one or more first proximal structures; and d) detecting a detectable signal provided by said one or more proximal structures.
18. The process for treating a material of claim 17 wherein at least one of said one or more first proximal structures undergoes a chemical change in response to said second energy transferred from said one or more semiconductor nanocrystal probes to said one or more first proximal structures.
19. A process for treating a material using one or more semiconductor nanocrystal probes to determine the presence of one or more detectable substances in said material which comprises:
a) contacting said material with one or more semiconductor nanocrystal probes, said one or more semiconductor nanocrystal probes each comprising, i) one or more semiconductor nanocrystals, each capable of, in response to exposure to a first energy, providing a second energy, ii) one or more first linking agents, to which said one or more semiconductor nanocrystals are linked, each of said one or more first linking agents capable of linking to 1) one or more second linking agents, or 2) one or more affinity molecules, and 3) one or more affinity molecules linked either to said one or more second linking agents or to said one or more first linking agents, each of said one or more affinity molecules capable of selectively bonding to said one or more detectable substances;
b) exposing said one or more semiconductor nanocrystal probes to said first energy; and c) detecting said second energy provided by said one or more semiconductor nanocrystals in said one or more semiconductor nanocrystal probes bonded to said one or more detectable substances in said material, wherein said material is flowed through one or more compartments transparent to i) said first energy to which said material is exposed, and ii) said second energy provided by said one or more semiconductor nanocrystal probes in response to exposure to said first energy.
20. The process for treating a material of claim 19 wherein said first energy is transferred from one or more proximal sources to said one or more semiconductor nanocrystal probes.
21. The process for treating a material of claim 20 wherein said second energy indicates the concentration of at least one of said one or more proximal sources.
22. The process for treating a material of claim 20 wherein said second energy indicates the distance between at least one of said one or more proximal sources and at least one of said one or more semiconductor nanocrystal probes.
23. The process for treating a material of claim 20 wherein said first energy to which said one or more semiconductor nanocrystals are exposed, is transmitted through said one or more proximal sources from an energy source separate from said one or more proximal sources.
24. The process for treating a material of claim 19 wherein at least one of said one or more first linking agents comprises a three dimensional structure.
25. A process for treating a material to determine the presence of one or more detectable substances in said material which comprises:
a) contacting said material with one or more semiconductor nanocrystal probes capable of bonding with said one or more detectable substances, if present, in said material, and capable of providing one or more detectable signals in response to exposure to energy, said one or more semiconductor nanocrystal probes comprising:
i) one or more semiconductor nanocrystals each capable of providing a detectable signal in response to exposure to energy;
ii) one or more first linking agents, to which said one or more semiconductor nanocrystals are linked, each of said one or more first linking agents capable of linking to:

1) one or more second linking agents; or 2) one or more affinity molecules; and iii) one or more affinity molecules linked either to said one or more second linking agents or to said one or more first linking agents, each of said one or more affinity molecules capable of selectively bonding to said one or more detectable substances;
b) optionally removing, from said material, any of said semiconductor nanocrystal probes not bonded to said one or more detectable substances; and c) exposing said material to energy capable of causing said one or more semiconductor nanocrystals to provide one or more detectable signals in response to said energy, indicative of the presence of said one or more detectable substances in said material; and d) detecting said one or more detectable signals provided by said one or more semiconductor nanocrystals in said one or more semiconductor nanocrystal probes.
CA 2366303 1997-11-25 2000-02-28 Semiconductor nanocrystal probes for biological applications Active CA2366303C (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US09259982 US6207392B1 (en) 1997-11-25 1999-03-01 Semiconductor nanocrystal probes for biological applications and process for making and using such probes
US09/259,982 1999-03-01
PCT/US2000/005257 WO2000055631A1 (en) 1999-03-01 2000-02-28 Semiconductor nanocrystal probes for biological applications

Publications (2)

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CA2366303A1 true true CA2366303A1 (en) 2000-09-21
CA2366303C CA2366303C (en) 2010-01-12

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US (11) US6207392B1 (en)
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CA (1) CA2366303C (en)
EP (3) EP2287614B1 (en)
WO (1) WO2000055631A1 (en)

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